Myoglobin

 
Myoglobin is the simplest type of oxygen carrying molecule in vertebrates. It consists of a single polypeptide chain bound to a heme group. The example shown on the left is sperm whale myoglobin. It shows the heme group edge on (gray) bound to a molecule of oxygen (red balls in the middle of the heme group on the right). The other oxygens, left and top, are part of the heme molecule.

The oxygen is bound to the iron atom at the center of the heme group. In the absence of oxygen this iron atom interacts with the side chains of two histidine residues in the myoglobin polypeptide chain. When oxygen binds it forms a bridge between one of the histidine residues (His-64) and the iron atom in the heme group.

Although the oxygen molecule is tightly bound in this configuration it is still capable of being released under the right conditions. Those conditions can be found inside cells that have become depleted in oxygen. Myoglobin is usually found in muscle cells in vertebrates where it plays a role in storing oxygen. The structure of myoglobin was determined by John Kendrew [Nobel Laureates].

Myoglobin is a member of a large family of globins. They include hemoglobin and similar oxygen carrying molecules in bacteria, plants, and other animals. The myoglobins have evolved from ancestral globins to specialize in oxygen storage inside cells.

©Laurence A. Moran and Pearson Prentice Hall 2007

Heme Groups

 
Monday's Molecule #37 is the heme group found in myoglobin and hemoglobin. The heme group consists of a ring structure, called a tetrapyrrole ring system, complexed to a central iron atom. There are many different kinds of these tetrapyrrole structures in cells. They are distinguished by slight changes in the chemistry of the ring system. This particular structure (left) is called protoporphyrin IX. The structure was originally determined by Hans Fischer [Nobel Laureate: Hans Fischer],

The red color of blood is due to the presence of the heme group, which absorbs visible light. Note that the pyrrole rings are linked by methene bridges (-CH=) to create a conjugated double bond system where electrons can be shared all across the ring. Not only does this mean that these rings can absorb photons, it also means that they can accommodate additional electrons without too much trouble.

This is why there are many heme proteins that are involved in oxidation-reduction reactions (reactions that transfer electrons from one substrate to another). For example, cytochrome c has a similar kind of heme group (right). Cytochrome c is a major player in membrane associated electron transport systems in bacteria and mitochondria and in photosynthesis.

Heme type molecules are always tightly bound to proteins. Such molecules are called prosthetic groups and there are two types. The heme in hemoglobin is bound by many weak interactions such as hydrogen bonds and van der Waals interactions. The heme in cytochrome c is an example of a covalently bound prosthetic group. It is attached to its protein by bonds between the edge of the porphyrin ring and cysteine (Cys) side chains in the protein.

Chlorophyll (left) is another type of tetrapyrrole ring molecule but it differs from most others because the central chelated metal ion is magnesium (Mg) instead of iron. Chlorophyll molecules absorb light very efficiently and that's why they play such an important role in photosynthesis. Photosynthesizing organisms—bacteria, algae, plants—have dozens (or hundreds) of chlorohyll molecules packed in their membranes.


©Laurence A. Moran and Pearson Prentice Hall 2007

Physicians Are "Science Professionals"

 
At least that's what the IDiots say [Medical Doctors a Fast Growing Segment of Darwin Doubting Science Professionals].

Who knew? I suppose we shouldn't be surprised if they think an M.D. degree makes you a "science professional." After all, these are some of the same people who think the Earth is only 10,000 years old.

UPDATE: Turns out that many of these medical doctors are actually dentists [Dentists Against Darwin]. Sheesh!

Your View of Evolution

 
The poll for August asks you to identify the person who comes closest to representing your view of evolution. Check out the left hand margin.

70% of Sandwalk Readers are Atheists

 
According to the latest poll (see left hand margin) 70% of Sandwalk readers are atheists (PZ would be proud.). 12% are agnostics—I guess Wilkins and Catshark figured out how to vote multiple times. Only 14% are believers. I wish there were more believers, it would make for more lively discussions.

Six of you are uncertain. Why?

Another Bad Review of The Edge of Evolution

PZ Myers draws attention to another review of Michael Behe's new book The Edge of Evolution [Behe gets another thumbs-down]. This review is published in the July issue Discover magazine [The Simplistic Manifesto]. The author is Cory S. Powell.

I disagree with PZ. This is not a good review. Actually, it's a very bad review. Like many of the published reviews of The Edge of Evolution the author seems to have been reading a far different book than the one I read. Powell says,

To reach this conclusion, Behe makes a number of invalid assumptions about how molecules evolve and interact. He alleges that, because many functional adaptations require multiple changes in proteins, two or more mutations must occur together at the same time in the same gene and only rarely can several mutations "sequentially add to each other to improve an organism’s chances of survival." But in fact natural selection does work on transitional forms, as molecules and traits evolve stepwise. Stepwise evolution has been well documented; one good instance of this is the emergence of color vision. Mutations add up little by little, leading to major changes to proteins over time.

The essence of Behe's argument is not that it's impossible to evolve a double mutation if each one is beneficial. The whole point of the book is that stepwise evolution requires that each step is beneficial. The evidence, according to Behe, shows that many cases involving double mutations involve intermediates that are disadvantagous. Thus, the double mutant had to arise in a single step and this is highly unlikely.

Behe isn't always as clear as he should be but he does make it perfectly clear that he accepts the mechanism that Powell describes. Thus, Powells' criticism is inappropriate and this makes it a bad review. Apparently Powell didn't read the section on the evolution of antifreeze proteins in fish (pp. 77-81) where Behe describes each of the many steps that lead to the modern antifreeze proteins.

Each step would have given the fish some protection against freezing water. Thus, Behe concludes,

Even though we haven't directly observed it, the scenario seems pretty convincing as an example of Darwinian evolution by natural selection. It's convincing because each of the steps is tiny&mdash'no bigger than the step that yielded the sickle cell mutation n humans—and each step is an improvement.

The Discovery review points out that complex combinations of mutations can arise in a stepwise manner by standard Darwinian mechanisms. It implies that Behe never thought of this in his book but that's total nonsense. Of course he did. Behe doesn't deny that phenotypes requiring multiple steps can be produced by random mutations, as long as each step is beneficial. The essence of his argument is that it's impossible to generate phenotypes that require multiple random mutations if the intermediates aren't beneficial.

I'm not arguing that Behe is correct. In fact, I'm preparing a series of postings that will challenge some of his ideas. What I'm objecting to is the mischaracterization of Behe's arguments in many of the published reviews. If you're going to criticize Behe then challenge the argument he makes in the book; namely, that most stepwise pathways are impossible because the intermediates are less fit than their parents.

Powell makes another common mistake in his review. He says,

Behe makes another big, related error in the way he interprets how proteins work together. He contends that for even three proteins to evolve in a cooperative association is wildly improbable, "beyond the edge of evolution." Within a protein, five or six amino acids (components of proteins) need to change simultaneously for it to bond with another protein, according to Behe. From this he concludes that it is impossible for proteins’ interaction to evolve, again requiring life to have been programmed for success from the start. Plenty of evidence contradicts this assertion, however. Many proteins within cells interact with other proteins in ways in which only two or three amino acids are critical for binding.

Behe admits that you may only need three or four selected changes in order to generate a new binding site (p. 114). He agrees that the evolution of a single binding site is within reach of evolution but the simultaneous generation of two binding sites is beyond the edge of evolution because the probabilities are so low. The point is that there are many complexes that require the interaction of several different proteins and the intermediates—where only two proteins interact—are not beneficial. Refuting Behe's real arguments requires a little more effort than the superficial criticism of arguments that Behe is not making.

Powell continues,

Such simple binding sites can arise frequently in proteins. And such interactions form the networks that regulate all sorts of physiological processes in cells and organisms. Cell biologists and biochemists are increasingly finding that, in truth, protein interactions and networks are easy to evolve. Behe should know this—but he has a long history of alleging evolutionary impossibilities and ignoring the scientific literature.

Powell is completely missing the point here. Behe does not deny that such complexes exist, nor does he deny that they evolved in the sense that they arose in organisms whose ancestors didn't have them. Once the mutations occurred, they became fixed in the population by natural selection. Furthermore, Behe does not deny that these networks are "easy to evolve." In fact, they are so "easy to evolve" that they cannot be explained by natural selection acting on random mutations as "Darwinism" requires. Thus, mutations cannot be random.

You don't refute Behe by pointing to examples of evolution by common descent or natural selection; this includes evolution of protein complexes. That's not the point. The point is that "Darwinian" evolution, according to Behe, must require small steps where each step is beneficial and this cannot be demonstrated. Indeed, in many cases the intermediates will likely be detrimental. The conclusion is that multiple mutations have to occur simultaneously as in some drug resistance. For most populations the probability of this happening by random mutation is very small. The fact that it happened is evidence of directed mutation, or so Behe thinks.

In order to show that Behe is wrong you have to demonstrate that his understanding of evolution (i.e., "Darwinism") is wrong and this has led him to false conclusions about probabilities. Many reviewers have failed to do this, possibly because they accept Behe's version of Darwinism.

You can read Michael Behe's responses to his reviewers on the Amazon.com site [Michael Behe's Amazon Blog]. I think it's fair to say that Behe makes some good points (and many bad ones) when he accuses his reviewers of misrepresentation.

Virtual Toronto

 
Here's a site that combines an interactive map of Toronto with images from selected streets [Toronto Virtual City]. The photograph (left) shows the entrance to my building on the University of Toronto campus. The view is looking north from College St.

The satellite view is about two years old. It was taken when the new building was still under construction so the street level image doesn't match the satellite view.

Hmmm ... that reminds me. How come we don't see any more postings where we have to identify a university campus? I forgot which blog that was on.

[Hat Tip: Monado]

Gene Genie #12

 


Gene Genie #12 has been posted at My Biotech Life [Gene Genie #12 aka The Dozen].

The image is from the article on snpedia [WikiPedia Meets Genetics]. Read about how you can access the personal genome of Jim Watson and Craig Ventor.

Monday's Molecule #37

 
Today's molecule looks complicated but it has a very simple name. The short common name of this molecule is not sufficient—you have to supply the correct biochemical name that distinguishes this molecule from similar ones found inside all cells. You're more than welcome to supply the complete IUPAC name if you know it.

There's an indirect connection between this Monday's Molecule and Wednesday's Nobel Laureate(s).

The reward (free lunch) goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There's only one (Marc) ineligible candidates for this Wednesday's reward since many recent winners haven't collected their prize. The prize is a free lunch at the Faculty Club.

Comments will be blocked for 24 hours. Comments are now open.

Canadian Dinosaur Coins

 
The Royal Canadian Mint has dinosaur coins for sale. Here's a picture of the first one. It shows a fossil Parasaurolophus, a crested, duck-billed species from Alberta.

Future coins will depict Triceratops (2009); Tyrannosaurus rex (2009); and Dromaeosaurus (2010). The face value of the coins is $4 (CDN)—that's currently about $3.80 in US currency but it will be about $4.60 by the time the last coin is issued unless the US dollar stops falling. (Getting out of Iraq would help.)

Only 20,000 coins are being minted. The finish on the "fossil" image is impossible to reproduce exactly so each coin will be slightly different in tone and color. You can buy them for $39.95 (CDN).

How many people know what "D.G. Regina" stands for? (Hint: it's not an atheist slogan.)

The OUT Campaign

 
RichardDawkin.net has started something called the The OUT Campaign. The goal is to encourage all non-believers (atheists) to come out of the closet and make their rejection of religious superstition known. You're supposed to use the red "A" as a symbol to declare that you are an atheist. Several bloggers have put it on their website.

I do not believe in God. I am an atheist. However, the fact that I don't believe in something is often the only thing I have in common with other atheists. It seems a bit silly to form a club based only on what you don't believe in. It would be like having a club for everyone who doesn't believe in Bigfoot, or Santa Claus.

So, while I am happy to announce my preference for rationalism over superstition and proud to be an atheist. I won't be joining any organization based on a negative. I am a proud member of Skeptics Canada and The Centre for Inquiry, Toronto because they stand for something positive.

[Hat Tip: PZ Myers]

The Aliens Are Coming

 
Friday's Urban Legend: False

			The following email message is going the rounds. ALIENS ARE COMING TO ABDUCT ALL THE GOOD LOOKING AND SEXY PEOPLE. YOU WILL BE SAFE, I'M JUST EMAILING TO SAY GOODBYE. We know it's false because I'm still here.

Theme: Deoxyribonucleic Acid (DNA)

 
THEME

Deoxyribonucleic Acid (DNA)

1. Wellcome Trust Images


2. A Strange Molecule


3. Monday's Molecule #35 (ethidium)


4. DNA Is a Polynucleotide


5. Tautomers of Adenine, Cytosine, Guanine, and Thymine


6. Nucleotides Can Adopt Many Different Conformations


7. Nobel Laureates: Francis Crick, James Watson, and Maurice Wilkins


8. The Chemical Structure of Double-Stranded DNA


9. The Three-Dimensional Structure of DNA


10. The Story of DNA (Part 1) Where Rosalind Franklin Teaches Jim and Francis Something about Basic Chemistry


11. Ethidium Bromide Binds to DNA


12. Rosalind Franklin Announces the Death of the Helix


13. Nobel Laureates 1962


14. The Story of DNA (Part 2)Where Jim and Francis Discover the Secret of Life


15. DNA With Parallel Strands


16. Measuring Stacking Interactions


17. Are You as Smart as a Third Year University Student?


18. Rosalind Franklin's Birthday


19. The Watson & Crick Nature Paper (1953)


20. The Franklin & Gosling Nature Paper (1953)


21. The Wilkins, Stokes and Wilson Nature paper (1953)


22. Ethidium Bromide Is a Dangerous Chemical


23. Jim Watson on the Discovery of the Double Helix


24. DNA Tatoo


25. DNA Polymerase I and the Synthesis of Okazaki Fragments


26. Play the DNA Double Helix Game

The Wilkins, Stokes and Wilson Nature paper (1953)

Wilkins published his work on the structure of DNA in the same issue of Nature as the Watson & Crick paper and the Franklin & Gosling paper. The coauthors on the wilkins paper were A.R. Stokes and H.R. Wilson. They were reunited in 1993 on the 40th anniversary of the publication as shown in the photo. (From left to right: Raymond Gosling, Herbert Wilson, Maurice Wilkins and Alec Stokes.)

A copy of the Wilkins, Stokes and Wilson paper is here.

The title of the paper "Molecular Structure of Deoxypentose Nucleic Acids" indicates that this is a paper that will discuss details and experimental results. This is a paper that emphasizes the similarities between X-ray diffraction patterns of DNA fibres from calf thymus, wheat germ, herring sperm, human, and T₂ bacteriophage. They also look at DNA in vivo by examining intact sperm heads, bacteriophage, and animal viruses. The authors conclude that all these DNA have the same general structure and that it is consistent with the model proposed by Watson & Crick.

The Franklin & Gosling Nature paper (1953)

Rosalind Franklin and Raymond Gosling published their results on the structure of DNA in a Nature paper that immediately followed the famous Watson & Crick paper [The Watson & Crick Nature Paper (1953)]. Franklin had completed the manuscript before traveling up to Cambridge to see the Watson & Crick model of DNA but she was able to make changes to her paper before submitting it in early April 1953. A PDF of the paper as it appeared in the journal is here and the original manuscript is here.

The title of the paper, "Molecular Configuration in Sodium Thymonucleate," gives us a clue to why this paper has been ignored and the Watson & Crick paper gets all the attention. The Franklin & Gosling paper is full of obscure references and equations and it's significance can only be recognized because of the paper that preceded it in the April 25th, 1953 issue of Nature. The writing style is ponderous and it does not convey any of the sense of excitement found in the Watson & Crick paper [see April 25, 1953: Three papers, three Lessons].

Franklin and Gosling conclude that DNA is "probably helical," the phosphate groups lie on the outside, and there are probably two strands. They state,

Thus our general ideas are not inconsistent with the model proposed by Watson and Crick in the preceding communication.

As is the case in the Watson & Crick paper, papers in the same issue of the journal are not specifically referenced. If you follow the link to the typed manuscript (above) you can see that this sentence was inserted by hand.

Franklin & Gosling acknowledge their colleagues at the end of the paper in the same manner we saw in the Watson & Crick paper.

We are grateful to Prof. J.T. Randall for his interest and to Drs. F.H.C. Crick, A.R. Stokes, and M.H.F. Wilkins for discussion.